The relationship between serum zinc levels and rheumatoid arthritis activity

Objective

Rheumatoid arthritis (RA) is one of the most prevalent chronic autoimmune diseases; it typically involves the hands, wrists, ankles, and eventually all joints. Some studies have reported that zinc serum levels are lower in patients with RA than in healthy individuals.

Materials and Methods

Seventy-nine patients with RAwere selected. The patients were all less than 75 years old and were diagnosed by a rheumatologist. Serum zinc levels were measured using the flame photometry method with a blood sample of 5 mL. The relationship between the average serum zinc level and disease activity was analyzed based on the DAS28 scoring scale for different RA groups. The significance threshold was set at p<0.05. Data analyses were implemented in SPSS 22.0.

Results

There was a significant inverse relationship between the serum zinc levels and disease activity. Chi-square tests were used to compare zinc serum levels with respect to disease activity. There were significant differences in zinc levels among three groups of patients with different levels of disease severity, such that disease activity increased as the serum zinc level decreased (p<0.001).

Conclusion

There was a significant inverse relationship between the serum zinc level and RA activity based on the DAS28 score. Therefore, it is recommended that mineral deficiencies should be addressed by optimizing the zinc supply along with other standard medications in order to reduce RA activity.

     

Binding studies of the anti‐retroviral drug,efavirenz to calf thymus DNA using spectroscopic and voltammetric techniques

Interactions between efavirenz (EFZ) with calf thymus DNA (CT‐DNA) were investigated in vitro under stimulated physiological conditions using multispectroscopic techniques, cyclic voltammetry viscosity measurement, and gel electrophoresis. Methylene blue and acridine orange dyes were used as spectral probes by fluorescence spectroscopy. Hypochromicity was observed in ultra‐violet (UV) absorption band of EFZ. Considerable fluorescence enhancement of EFZ was observed in the presence of increasing amounts of DNA solution and the binding constants (K_f) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters including enthalpy change (ΔH) and entropy change (ΔS) were calculated to be –304.78 kJ mol^–1 and –924.52 J mol^–1 K^–1 according to the van ’t Hoff equation, which indicated that reaction is predominantly enthalpically driven. In addition, UV/vis absorption titration of DNA bases confirmed that EFZ interacted with guanine and cytosine preferentially. Gel electrophoresis of DNA with EFZ demonstrated that EFZ also has the ability to cleave supercoiled plasmid DNA. Circular dichroism study showed stabilization of the right‐handed B form of CT‐DNA. All results suggest that EFZ interacts with CT‐DNA via an intercalative mode of binding. Copyright © 2015 John Wiley & Sons, Ltd.     

Chiral cationic polyamines for chiral microcapsules and siRNA delivery

Reported herein is the use of chiral cationic polyamines for two intriguing applications: fabrication of chiral covalently-linked microcapsules, and enantiospecific delivery of siRNA to Huh 7 cells. The microcapsules are easily fabricated from homochiral polymers, and the resulting architectures can be used for supramolecular chiral catalysis and many other potential applications. Enantiospecific delivery of siRNA to Huh 7 cells is seen by one ‘enantiomer’ of the polymers delivering siRNA with significantly improved transfection efficiency and reduced toxicity compared to the ‘enantiomeric’ polymer and commercially available transfection reagents. Taken together, the use of these easily accessible polyamine structures for diverse applications is highlighted in this Letter herein and can lead to numerous future research efforts.     

Dendritic cells loaded with exosomes derived from cancer stem cell-enriched spheroids as a potential immunotherapeutic option

Cancer stem cells (CSCs) are responsible for therapeutic resistance and recurrence in colorectal cancer. Despite advances in immunotherapy, the inability to specifically eradicate CSCs has led to treatment failure. Hence, identification of appropriate antigen sources is a major challenge in designing dendritic cell (DC)-based therapeutic strategies against CSCs. Here, in an in vitro model using the HT-29 colon cancer cell line, we explored the efficacy of DCs loaded with exosomes derived from CSC-enriched colonospheres (CSC_enr-EXOs) as an antigen source in activating CSC-specific T-cell responses. HT-29 lysate, HT-29-EXOs and CSC_enr lysate were independently assessed as separate antigen sources. Having confirmed CSCs enrichment in spheroids, CSC_enr-EXOs were purified and characterized, and their impact on DC maturation was investigated. Finally, the impact of the antigen-pulsed DCs on the proliferation rate and also spheroid destructive capacity of autologous T cells was assessed. CSC_enr-EXOs similar to other antigen groups had no suppressive/negative impacts on phenotypic maturation of DCs as judged by the expression level of costimulatory molecules. Notably, similar to CSC_enr lysate, CSC_enr-EXOs significantly increased the IL-12/IL-10 ratio in supernatants of mature DCs. CSC_enr-EXO-loaded DCs effectively promoted T-cell proliferation. Importantly, T cells stimulated with CSC_enr-EXOs disrupted spheroids' structure. Thus, CSC_enr-EXOs present a novel and promising antigen source that in combination with conventional tumour bulk-derived antigens should be further explored in pre-clinical immunotherapeutic settings for the efficacy in hampering recurrence and metastatic spread.     

Cytokines Alter IgA1 O-Glycosylation by Dysregulating C1GalT1 and ST6GalNAc-II Enzymes

IgA nephropathy (IgAN), the most common primary glomerulonephritis, is characterized by renal immunodeposits containing IgA1 with galactose-deficient O-glycans (Gd-IgA1). These immunodeposits originate from circulating immune complexes consisting of anti-glycan antibodies bound to Gd-IgA1. As clinical disease onset and activity of IgAN often coincide with mucosal infections and dysregulation of cytokines, we hypothesized that cytokines may affect IgA1 O-glycosylation. We used IgA1-secreting cells derived from the circulation of IgAN patients and healthy controls and assessed whether IgA1 O-glycosylation is altered by cytokines. Of the eight cytokines tested, only IL-6 and, to a lesser degree, IL-4 significantly increased galactose deficiency of IgA1; changes in IgA1 O-glycosylation were robust for the cells from IgAN patients. These cytokines reduced galactosylation of the O-glycan substrate directly via decreased expression of the galactosyltransferase C1GalT1 and, indirectly, via increased expression of the sialyltransferase ST6GalNAc-II, which prevents galactosylation by C1GalT1. These findings were confirmed by siRNA knockdown of the corresponding genes and by in vitro enzyme reactions. In summary, IL-6 and IL-4 accentuated galactose deficiency of IgA1 via coordinated modulation of key glycosyltransferases. These data provide a mechanism explaining increased immune-complex formation and disease exacerbation during mucosal infections in IgAN patients.     

Association of heat shock protein70-2 (HSP70-2) gene polymorphism with coronary artery disease in an Iranian population

Background

Coronary artery disease (CAD) is an inflammatory process and a major cause of mortality and morbidity. The (heat shock protein70-2) HSP70-2 gene is reported to be associated with coronary artery disease possibly by affecting the regulation of pro-inflammatory cytokines such as TNF-α. The association between CAD and the HSP70-2 gene + 1267A>G polymorphism has been studied in some populations but there are no data about this association in the Iranian population.

Aim

We have investigated the association between the HSP70-2 gene + 1267A>G polymorphism and angiographically defined CAD within an Iranian population.

Methods

We determined the presence of the HSP70-2 gene + 1267A>G polymorphism in 628 patients with CAD and 307 healthy individuals using PCR-RFLP. Of the patients, 433 (68%) had > 50% stenosis (CAD +) and the remaining 195 patients had < 50% stenosis (CAD −), based on coronary angiography. Angiogram positive patients were subdivided into three groups: those with single (n = 113), double (n = 134), and triple vessels (n = 186) disease.

Results

A significant higher frequency of AG + GG genotypes (G allele carriers) was observed in angiogram positive and angiogram negative groups compared to controls in a dominant analysis model of the HSP70-2 gene + 1267A>G position (51.2 vs. 43.2, P = 0.002, OR = 1.37) (51.0 vs. 43.2, P = 0.01, OR = 1.37). The allele frequency of the HSP70-2 G was also significantly higher in angiogram positive and angiogram negative groups compared to the control group (51.2 vs. 43.2, P = 0.002, OR = 1.37) (51.0 vs. 43.2, P = 0.01, OR = 1.37).

Conclusion

These results suggest that HSP70-2 + 1267 polymorphism may influence the risk of CAD in Iranian population, however further studies are needed to clarify the role of other HSP70-2 gene polymorphisms in the pathogenesis of the CAD.     

Sexual dysfunctions in patients with diabetes: a study from Iran

Background  

Diabetes mellitus is a chronic disease that causes short and long-term complications. This study aimed to investigate the prevalence of sexual dysfunctions (SD) among diabetic patients in Iran and to examine whether glycemic control has a role in SD.     

Correlation between the papanicolaou stain and the Wright-Giemsa stain in body fluids: a quality assurance study

OBJECTIVE: To compare the use of Papanicolaou and Wright-Giemsa stains for the evaluation of body fluids in cytology and hematology laboratories and determine whether other factors account for discrepancies in diagnosis. STUDY DESIGN: We retrospectively reviewed cytopathology reports of peritoneal, pleural, and cerebrospinal fluids received by hematology and cytology laboratories for 1 year. Cases were divided into 3 categories-benign, atypical, and malignant--and slides of discrepant diagnoses were reviewed. RESULTS: During this period, 198 of 3212 (0.61%) cases received by the hematology laboratory and 252 of 4402 (0.57%) cases received by the cytology laboratory were diagnosed as malignant or atypical. Of 3212 cases simultaneously received by the cytology and hematology laboratories, 17 diagnosed as malignant by hematology were diagnosed benign by cytology (sensitivity 96%). Sixteen cases diagnosed as malignant by cytology were diagnosed as benign by hematology (sensitivity 97%). No benign cases were diagnosed as malignant (specificity 100%). Review of the glass slides of the discrepant cases revealed 8 cases undercalled by hematology and 7 cases undercalled by cytology. CONCLUSION: Papanicolaou stain is superior for carcinoma and Wright-Giemsa stain for hematopoietic disorders, but used together they may reduce false negative results. Delays in processing, staining technique, and interobserver variability contribute to discrepancy.